1. Field of the Invention
This invention is directed to mixed alkyl cyanoacrylate compositions which are specifically formulated for topical application onto intact or broken human skin, preferably without the addition of a plasticizing agent to the composition.
2. References
The following publications, patent applications and patents are cited in this application as superscript numbers:
.sup.1 Rabinowitz, et al., Method of Surgically Bonding Tissue Together, U.S. Pat. No. 3,527,224, issued Sep. 8, 1970 PA0 .sup.2 Hawkins, et al., Surgical Adhesive Compositions, U.S. Pat. No. 3,591,676, issued Jul. 6, 1971 PA0 .sup.3 Halpern, et al., Adhesive for Living Tissue, U.S. Pat. No. 3,667,472, issued Jun. 6, 1972 PA0 .sup.4 Kronenthal, et al., Surgical Adhesives, U.S. Pat. No. 3,995,641, issued Dec. 7, 1976 PA0 .sup.5 Davydov, et al., Medical Adhesive, U.S. Pat. No. 4,035,334, issued Jul. 12, 1977 PA0 .sup.6 Waniczek, et al., Stabilized Cyanoacrylate Adhesives Containing Bis-Trialkylsilyl Esters of Sulfuric Acid, U.S. Pat. No. 4,650,826, issued Mar. 17, 1987 PA0 .sup.7 Barley, Methods of Retarding Blister Formation by Use of Cyanoacrylate Adhesives, U.S. Pat. No. 5,306,490 issued Apr. 26, 1994 PA0 .sup.8 Barley, et al., Methods to Prevent Irritation Arising from Casts and Prosthesis, U.S. Pat. No. 5,653,769 issued Aug. 5, 1997 PA0 .sup.9 Tighe, et al., Use of Cyanoacrylate Adhesives for Providing a Protective Barrier Film for the Skin, U.S. Pat. No. 5,580,565 issued Dec. 3, 1996 PA0 .sup.10 Askill, et al., Methods for Draping Surgical Incision Sites, U.S. Pat. No. 5,730,994 issued Mar. 24, 1998 PA0 .sup.11 Greff, et al., Cyanoacrylate Adhesive Compositions, U.S. Pat. No. 5,480,935 issued Jan. 2, 1996
All of the above publications, patent applications and patents are herein incorporated by reference in their entirety to the same extent as if each individual publication, patent application or patent was specifically and individually indicated to be incorporated by reference in its entirety.
3. State of the Art
Cyanoacrylate esters are well known in the art and can be represented by formula I: ##STR1## wherein R is an alkyl group or other suitable substituent forming the ester component of the molecule. Such cyanoacrylates are disclosed, for example, in U.S. Pat. Nos. 3,527,224, 3,591,676; 3,667,472; 3,995,641; 4,035,334; and 4,650,826..sup.1-6 Typically, when applied onto living tissue, the R substituent is most often lower alkyl (e.g., C.sub.1 to C.sub.8) and the corresponding alkyl cyanoacrylate esters are liquids at room temperature.
Heretofore disclosed uses for topical application of polymerizable cyanoacrylate compositions comprising lower alkyl cyanoacrylate esters to mammalian skin include application onto intact skin in order to form a polymer layer which inhibits blister formation;.sup.7 which inhibits irritation arising from prosthetic devices;.sup.8 which inhibits skin irritation and infection due to incontinence;.sup.9 which can be used as a surgical drape;.sup.10 and the like. The liquid character of these compositions assist in application onto the skin and in the formation of a thin unbroken polymer film on the skin.
It is well known, however, that lower alkyl cyanoacrylate esters do not form a flexible polymer film on mammalian skin but, rather, a brittle polymer film is formed which lacks long term integrity due to cracking, etc. Accordingly, compositions comprising lower alkyl cyanoacrylate esters are typically formulated to comprise a compatible plasticizer which imparts flexibility to the polymer film such that the integrity of the polymer coating is not compromised..sup.11 Suitable plasticizers heretofore disclosed in the art for use in such cyanoacrylate compositions include dioctyl phthlate, acetyl tri-n-butyl citrate, and the like..sup.11
The use of plasticizers in such compositions poses problems such as compatibility of the plasticizer with the composition and compatibility of the plasticizer with mammalian skin..sup.11 In fact, incomplete compatibility of the plasticizer with mammalian skin as measured by skin irritation is often balanced by the need to impart flexibility to the polymer film and plasticizers are often selected based on there ability to impart only minimal skin irritation.
Notwithstanding issues arising from the compatibility of the plasticizer in a cyanoacrylate composition, any plasticizer used in such cyanoacrylate compositions acts as a diluent which results in weakening of the adhesion of the resulting polymer film to the skin. Moreover, the plasticizer is not incorporated into the polymer backbone but, rather, is integrated into the polymer film and there is a maximum amount of plasticizer which can be added to the cyanoacrylate composition while still allowing the composition to form such a polymer film on the skin. In this regard, small molecule plasticizers can be leached out of the polymeric film.
As is apparent, the incorporation of a plasticizer into the cyanoacrylate composition often comprises balancing the benefits versus the detriments arising from the use of the plasticizer. Contrarily, cyanoacrylate compositions which result in the formation of a flexible cyanoacrylate polymer film on mammalian skin without the use of a conventional plasticizer would be particularly desireable since the detrimental aspects arising from incorporation of the plasticizer would be obviated. Preferably, for ease of delivery, the composition comprising the C.sub.1 to C.sub.8 alkyl cyanoacrylate ester should be a liquid.